SEQUENTIAL ADMINISTRATION OF INTERLEUKIN-6 AND GRANULOCYTE-COLONY STIMULATING FACTOR IN NEWBORN RATS - MODULATION OF NEWBORN GRANULOPOIESIS AND THROMBOPOIESIS

During states of increased demand, neonatal host defense is characterized by dysregulation of granulopoiesis, resulting in a high incidence of neutropenia. This study investigated the modulation of neonatal rat hematopoiesis by 14-d administration of recombinant human (rh) IL-6, rh-granulocyte-colony stimulating factor (G-CSF), or sequential combination of rhIL-6 and rhG-CSF. Specifically, newborn Sprague-Dawley rats were treated with either rhIL-6 (5-mu-g/kg/d for 14 d), rhG-CSF (5-mu-g/kg/d for 14 d), rhIL-6 for 7 d followed by rhG-CSF for 7 d, PBS/BSA for 7 d followed by rhG-CSF for 7 d, or PBS/BSA for 14 d. RhIL-6 alone significantly increased the peripheral platelet count during the latter part of the 2nd wk of administration (d 13: 980 +/- 42 versus 716 +/- 23 x 10(3)/mm3) (p = < 0.001) (mean +/- SEM). Treatment with rhIL-6 for 7 d followed by rhG-CSF significantly increased the peripheral neutrophil count compared with 7 d of PBS/BSA and 7 d of G-CSF (d 14 absolute neutrophil count 4888 +/- 12 versus 2720 +/- 317/mm3) (p = < 0.05). Similarly, sequential rhIL-6/rhG-CSF significantly increased the d-14 bone marrow neutrophil storage pool (9873 +/- 882 versus 3564 +/- 159/mm3) (p = < 0.005). Lastly, sequential rhIL-6/rhG-CSF induced the highest increase in bone marrow (p < 0.01) and liver/spleen CFU-GM pool (p < 0.001) compared with any other treatment group. These studies suggest that rhIL-6 alone is associated with a significant increase in the neonatal platelet count. The sequential combination of rhIL-6 followed by rhG-CSF may also induce significant increases in neonatal peripheral neutrophilia, bone marrow neutrophil storage pools, and bone marrow and liver/spleen myeloid progenitor pools. This sequential combination has been demonstrated to enhance neonatal hematopoiesis.